Titanium dioxide (TiO₂) is considered as an inert and safe material and has been used in many applications for decades. However, with the development of nanotechnologies TiO₂ nanoparticles, with numerous novel and useful properties, are increasingly manufactured and used. Therefore increased human and environmental exposure can be expected, which has put TiO₂ nanoparticles under toxicological scrutiny. Mechanistic toxicological studies show that TiO₂ nanoparticles predominantly cause adverse effects via induction of oxidative stress resulting in cell damage, genotoxicity, inflammation, immune response etc. The extent and type of damage strongly depends on physical and chemical characteristics of TiO₂ nanoparticles, which govern their bioavailability and reactivity. Based on the experimental evidence from animal inhalation studies TiO₂ nanoparticles are classified as “possible carcinogenic to humans” by the International Agency for Research on Cancer and as occupational carcinogen by the National Institute for Occupational Safety and Health. The studies on dermal exposure to TiO₂ nanoparticles, which is in humans substantial through the use of sunscreens, generally indicate negligible transdermal penetration; however data are needed on long-term exposure and potential adverse effects of photo-oxidation products. Although TiO₂ is permitted as an additive (E171) in food and pharmaceutical products we do not have reliable data on its absorption, distribution, excretion and toxicity on oral exposure. TiO₂ may also enter environment, and while it exerts low acute toxicity to aquatic organisms, upon long-term exposure it induces a range of sub-lethal effects.

In a 2017 study published in Scientific Reports, researchers exposed rats to human-relevant levels of E171 to examine the effects of intestinal inflammation and carcinogenesis. They saw that “a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model.” They continued: “Stimulation of immune cells isolated from Peyer’s Patches [which are clusters of lymphoid follicles found in the intestine] showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased,” researchers wrote. “A 100-day titanium dioxide treatment promoted colon microinflammation and initiated preneoplastic lesions.” The scientists concluded: “These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources.”

Blanc de lithopone, blanc de Comines, zincolith, blanc de Charlton, blanc de Becton, tithopone

Other food manufacturers use titanium dioxide to absorb water and keep moisture from clumping or degrading, Paul Westerhoff, PhD, an environmental engineer at Arizona State University who researches the biological and cellular effects of titanium dioxide, told Health.

In addition to its outstanding properties, lithopone has excellent stability, weather resistance and chemical inertness. This makes it suitable for a wide range of applications, even under harsh environmental conditions. You can rely on lithopone to stand the test of time, maintaining its luster and performance for years to come.

Australian researchers examined how titanium dioxide as a food additive affected gut microbiota in mice by orally administering it in drinking water. The study, published in the journal Frontiers in Nutrition in 2019, found the treatment could “alter the release of bacterial metabolites in vivo and affect the spatial distribution of commensal bacteria in vitro by promoting biofilm formation. We also found reduced expression of the colonic mucin 2 gene, a key component of the intestinal mucus layer, and increased expression of the beta defensin gene, indicating that titanium dioxide significantly impacts gut homeostasis.” The changes were then linked to colonic inflammation, along with a higher expression of inflammatory cytokines, which are signal proteins that help with regulation. The researchers concluded that titanium dioxide “impairs gut homeostasis which may in turn prime the host for disease development.”

This route affords a product that is 29.4 wt % ZnS and 70.6 wt % BaSO₄. Variations exist, for example, more ZnS-rich materials are produced when zinc chloride is added to the mixture of zinc sulfate and barium sulfide.^[1]

In food products, E171 is not a singular ingredient; it’s always combined with other ingredients (e.g., proteins and fats) in the food product. Digesting food is a slow process for the body compared to drinking a beverage, which passes much faster through the body.